In a quadrupole mass spectrometer, an amount of voltage corresponding to the mass-to-charge-ratio (m/z) of a target ion to be analyzed (this voltage is composed of a DC voltage and a radio-frequency voltage combined together) is applied to a quadrupole mass filter to selectively allow the target ion to pass through the quadruple mass filter and be detected by a detector. In many cases, when the system is controlled so as to selectively allow an ion having a target mass-to-charge ratio to pass through the quadruple mass filter, a discrepancy occurs between the target mass-to-charge ratio and the mass-to-charge ratio of the actually detected ion, due to mechanical errors in the quadrupole mass filter, variations in the characteristics of electric circuits, conditions of the use environment, and other factors. To correct this discrepancy in the mass-to-charge ratio, a mass calibration (i.e. calibration of the mass-to-charge ratio) is normally performed before the measurement.
In the mass calibration task, as described in Patent Literature 1, a measurement is initially performed using a standard sample containing a component whose theoretical value of the mass-to-charge ratio is previously known. The obtained measured value of the mass-to-charge ratio is compared with the theoretical value to determine the mass deviation at that mass-to-charge ratio, and this mass deviation is stored as a calibration value in a memory device. Later on, in the measurement of a target sample, a controller reads the calibration value corresponding to the target mass-to-charge ratio from the memory device and corrects the voltage applied to the quadrupole mass filter using the calibration value so that the mass deviation will be zero. Consequently, an ion having the target mass-to-charge ratio is selectively allowed to pass through the quadrupole mass filter, to eventually arrive at and be detected by the detector.
Meanwhile, a mass spectrometric technique called the MS/MS analysis is commonly used for the purpose of identifying substances having high molecular weights and analyzing their structures. There are various configurations of mass spectrometers for performing MS/MS analyses, among which the triple quadrupole mass spectrometer is popularly used due to its comparatively simple structure and inexpensiveness.
As disclosed in Patent Literature 2 and other documents, a triple quadrupole mass spectrometer normally has a front-stage quadrupole mass filter (which is hereinafter called the “front quadrupole”) and a rear-stage quadrupole mass filter (which is hereinafter called the “rear quadrupole”), with a collision cell (collision chamber) provided in between for breaking ions into fragments by collision induced dissociation (CID). Inside this collision cell, an ion guide with four (or more) poles is provided to transport ions while focusing them.
When various ions produced from a sample are introduced into the front quadrupole, the front quadrupole selectively allows only an ion having a specific mass-to-charge ratio to pass through it as a precursor ion. Meanwhile, CID gas (e.g. argon gas) is introduced into the collision cell. The precursor ion introduced into this collision cell collides with the CID gas and undergoes dissociation to be broken into various product ions. The precursor ion and various product ions are focused by the effect of the radio-frequency electric field formed by the quadrupole ion guide. When the various product ions produced by the CID are introduced into the rear quadrupole, the rear quadrupole selectively allows only a product ion having a specific mass-to-charge ratio to pass through it. The product ion which has been allowed to pass through the rear quadrupole arrives at and is detected by the detector.
Such a triple quadrupole mass spectrometer is capable of performing MS/MS analyses in various modes, such as the multiple reaction monitoring (MRM) measurement, product-ion scan measurement, precursor-ion scan measurement, and neutral-loss scan measurement.
In the MRM measurement, the mass-to-charge ratio of the ion which is allowed to pass through is fixed in each of the front and rear quadrupoles to measure the intensity of a specific product ion derived from a specific precursor ion. In the product-ion scan measurement, while the mass-to-charge ratio of the ion which is allowed to pass through the front quadrupole is fixed at a certain value, the mass-to-charge ratio of the ion which is allowed to pass through the rear quadrupole is varied to scan a predetermined range of mass-to-charge ratios. By this operation, a mass spectrum of product ions derived from a specific precursor ion is obtained.
The precursor-ion scan measurement is the opposite of the product-ion scan measurement: While the mass-to-charge ratio of the ion which is allowed to pass through the rear quadrupole is fixed at a certain value, the mass-to-charge ratio of the ion which is allowed to pass through the front quadrupole is varied to scan a predetermined range of mass-to-charge ratios. By this operation, a mass spectrum of precursor ions which generate a specific product ion is obtained. In the neutral-loss scan measurement, a mass scan over a predetermined mass range is performed in each of the front and rear quadrupoles while constantly maintaining the difference between the mass-to-charge ratio of the ion passing through the front quadrupole and that of the ion passing through the rear quadruple (i.e. the neutral loss). By this operation, a mass spectrum of precursor ions/product ions having a specific neutral loss is obtained.
Naturally, the triple quadrupole mass spectrometer can also be used to perform a normal scan measurement or selected ion monitoring (SIM) measurement in which no CID is performed in the collision cell. In this case, the operation of selecting an ion according to its mass-to-charge ratio is not performed in one of the front and rear quadrupoles; all the ions are allowed to pass through that quadrupole.
Since the two (front and rear) quadrupole mass filters are thus provided, the triple quadrupole mass spectrometer requires the mass calibration to be performed independently for each of the front and rear quadrupoles in order to improve the capability of selecting the precursor or product ion. In the case of conventional triple quadrupole mass spectrometers, the mass calibration information for MS/MS analyses is normally prepared independently for each of the front and rear quadrupoles based on a measurement result obtained by an MS analysis performed at a certain low level of scan speed using a standard sample. However, a problem exists in that, if the mass calibration information obtained in this manner is used as a basis for the mass calibration, the discrepancy in the mass-to-charge ratio axis in the mass spectrum will increase with an increase in the scan speed in some measurement modes, such as the precursor-ion or neutral-loss scan measurement.
Similarly to the mass calibration, the adjustment of the mass-resolving power is also performed using a measurement result obtained by an MS measurement performed at a certain low level of scan speed using a standard sample. This has the problem that the mass-resolving power decreases (i.e. the peak width of a peak profile corresponding to a single component increases) with an increase in the scan speed in some measurement modes, such as the precursor-ion scan or neutral-loss scan, or even if the mass-resolving power does not decrease, the sensitivity significantly decreases due to the decrease in the amount of ions passing through.
In recent years, substances to be analyzed have been more and more complex, while currently there is a strong demand for improving the efficiency of the analyzing task as well as enhancing the quality of the analysis. For example, in a system having a liquid chromatograph (LC) coupled with a triple quadrupole mass spectrometer, a product-ion scan measurement triggered by an MRM measurement or normal scan measurement may be performed in order to obtain structural information in conjunction with the measurement of the molecular weights of various components contained in a sample. In such a case, it is necessary to increase the scan speed and repeat the scan measurement with a shorter cycle of time, in order to ensure an adequate number of data points per one peak or to perform the product-ion scan measurement for both positive and negative ions as well as under multiple conditions with different amounts of collision energy. To meet such needs, increasing the mass-scan speed is indispensable, which makes the aforementioned problems more noticeable, such as the discrepancy in the mass-to-charge ratio axis and the decrease in the mass-resolving power.
Therefore, in Patent Literature 3, the present inventor has proposed a triple quadrupole mass spectrometer having a calibrating function in which mass calibration information showing the relationship between the mass-to-charge ratio and the calibration value (or resolution-adjusting value) with the scan speed as the parameter is stored for each measurement mode of the MS analysis and MS/MS analysis, and the mass-to-charge ratio of the ion to be detected by the detector is calibrated by driving each of the front and rear quadrupoles using the mass calibration value (or resolution-adjusting value) corresponding to the measurement mode to be performed and the scan speed specified. With the triple quadrupole mass spectrometer described in Patent Literature 3, it is possible to reduce the discrepancy in the mass-to-charge ratio axis of the mass spectrum or the decrease in the mass-resolving power and obtain a mass spectrum with a high level of mass accuracy or high level of mass resolution even in the case of performing an MS/MS analysis including a high-speed scan.